The mechanism and control of fatty acid synthesis in animal cells and fungi will be investigated. Present evidence indicates that the fatty acid synthetases from eucarotic cells have molecular weight of 400,000-500,000 (avian and mammalian enzymes) or about 2,000,000 (yeast and other fungi enzymes). The synthetases are complexes made up of two subunits of single polypeptide chains of 200,000-220,000 daltons each. Since the subunits have many of the component activities involved in fatty acid synthesis, then the polypeptides are multifunctional enzymes which contain numerous active sites on a single polypeptide chain. Studies will be carried out in order to determine whether the two subunits of the fatty acid synthetase are identical. Recent studies indicate that animal synthetases contain two prosthetic groups (4'-phosphopantetheine) per mole of enzyme instead of the one prosthetic group previously reported. A scheme consistent with these structural findings is proposed for the fatty acid synthetases in which both the acyl and malonyl groups are bound to the prosthetic group prior to condensation to form the beta-ketoacyl derivatives. Further evidence to support this hypothesis will be obtained including the controlled cleavage of the synthetase labeled with radioactive acyl or malonyl groups. Also, we plan to isolate the catalytic centers of the acylases free from other activities by techniques involving proteolysis and protein fractionation. BIBLIOGRAPHIC REFERENCES; Arslanian, M.J., Stoops, J.K., Oh, Y.H. and Wakil, S.J.,"On the 4'-Phosphopantetheine Content of Chicken and Rat Liver Fatty Acid," J. Biol. Chem., 251, 3194-3196 (1976). Okuyama, H., Yamada, K., Ikezawa, H., and Wakil, S.J., "Factors Affecting the Acyl Selectivities of Acyl Transferases in Escherichia coli," J. Biol. Chem., 251, 2487-2492 (1976).